Glutamine catabolism supports amino acid biosynthesis and suppresses the integrated stress response to promote photoreceptor survival.

Photoreceptor loss results in vision loss in many blinding diseases, and metabolic dysfunction underlies photoreceptor degeneration. So, exploiting photoreceptor metabolism is an attractive strategy to prevent vision loss. Yet, the metabolic pathways that maintain photoreceptor health remain largely unknown. Here, we investigated the dependence of photoreceptors on Gln catabolism. Gln is converted to glutamate via glutaminase (GLS), so mice lacking GLS in rod photoreceptors were generated to inhibit Gln catabolism. Loss of GLS produced rapid rod photoreceptor degeneration. In vivo metabolomic methodologies and metabolic supplementation identified Gln catabolism as critical for glutamate and aspartate biosynthesis. Concordant with this amino acid deprivation, the integrated stress response (ISR) was activated with protein synthesis attenuation, and inhibiting the ISR delayed photoreceptor loss. Furthermore, supplementing asparagine, which is synthesized from aspartate, delayed photoreceptor degeneration. Hence, Gln catabolism is integral to photoreceptor health, and these data reveal a novel metabolic axis in these metabolically-demanding neurons.

Radioactive iodine administration is not associated with improved disease-specific survival in classic papillary thyroid carcinoma greater than 4 cm confined to the thyroid.

BACKGROUND: We aimed to evaluate the impact of radioactive iodine on disease-specific survival in intrathyroidal (N0M0) papillary thyroid carcinoma >4 cm, given conflicting data in the American Thyroid Association guidelines regarding their management. METHODS: The Surveillance, Epidemiology, and End Results database was queried for N0M0 classic papillary thyroid carcinoma >4 cm. Kaplan-Meier estimates were performed to compare disease-specific survival between radioactive iodine-treated and untreated groups. A multivariable Cox regression was performed to identify predictors of disease-specific survival. RESULTS: There were more patients aged ≥55 (41.7% vs 32.3%, P = .001) and fewer multifocal tumors (25.3% vs 30.6%, P = .006) in the no radioactive iodine group. Ten-year disease-specific survival was similar between the radioactive iodine treated and untreated groups (97.2% vs 95.6%, P = .34). Radioactive iodine was not associated with a significant disease-specific survival benefit (adjusted hazard ratio = 0.78, confidence interval [0.39-1.58], P = .49). Age ≥55 (adjusted hazard ratio = 3.50, confidence interval [1.69-7.26], P = .001) and larger tumor size (adjusted hazard ratio = 1.04, confidence interval [1.02-1.06], P < .001) were associated with an increased risk of disease-specific death. Subgroup analyses did not demonstrate improved disease-specific survival with radioactive iodine in patients ≥55 and in tumors >5 cm. CONCLUSION: Adjuvant radioactive iodine administration in classic papillary thyroid carcinoma >4 cm confined to the thyroid did not significantly impact disease-specific survival. Thus, these patients may not require routine treatment with adjuvant radioactive iodine.

Chemoprofiling and medicinal potential of underutilized leaves of Cyperus scariosus.

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

Chronic Widespread Spinal Pain (CWSP) Alleviated With Chiropractic Biophysics®: A Case Report With Three-Year Follow-Up.

The aim of this case report is to provide clinicians with an option for the treatment of spine pain, spine disorders caused or complicated by abnormal spine alignment, and failed prior interventions for pain and suffering with a conservative protocol. Multi-decade chronic widespread pain (CWSP), low back pain (LBP) headache (HA), and neck pain (NP) cause significant disability and reduced quality of life across all socio-economic and societal categories. Treatment options for decades-old long-term pain with good outcomes are uncommon with non-surgical and surgical interventions. Herein is a single case of positive outcomes with Chiropractic BioPhysics® (CBP®)protocol and long-term follow-up. A 60-year-old male with a lifting injury working on a farm at age 12 suffered for decades with LBP, mid-back pain (MBP), NP, HAs, radiculopathy, and poor health-related quality of life (HRQoL). Prior over-the-counter (OTC) medications with diminishing results over 48 years were reported. The patient had multiple abnormal patient-reported outcomes (PROs) as well as measured postural and spine structural abnormalities at the initial assessment. Following 12 treatments, PROs and other measures improved dramatically. Continued brief treatment showed continued progress followed by no treatment beyond continued home exercises and home postural orthoses. All subjective and objective outcome measures improved at one-year follow-up and remained long-term. Improvements in sagittal and coronal postural balance with improved spine alignment, better PROs, and measurably improved HRQoLs were found at one- and three-year follow-ups from the initial evaluation. Chronic NP, LBP, MBP, and extremity pain with altered sensation, loss of function, and failed drug therapy are common across the globe and combined represent the greatest contributors to disability and the global burden of disease (GBD). Economic, efficacious, repeatable, and reliable methods for treating pain will reduce GBD and improve PROs. Larger studies of CBP® methods for multi-decade chronic pain are challenging; however, continued case reports and RCTs for similar conditions are warranted.

Medical and genetic correlates of long-term buprenorphine treatment in the electronic health records.

Despite the benefits associated with longer buprenorphine treatment duration (i.e., >180 days) (BTD) for opioid use disorder (OUD), retention remains poor. Research on the impact of co-occurring psychiatric issues on BTD has yielded mixed results. It is also unknown whether the genetic risk in the form of polygenic scores (PGS) for OUD and other comorbid conditions, including problematic alcohol use (PAU) are associated with BTD. We tested the association between somatic and psychiatric comorbidities and long BTD and determined whether PGS for OUD-related conditions was associated with BTD. The study included 6686 individuals with a buprenorphine prescription that lasted for less than 6 months (short-BTD) and 1282 individuals with a buprenorphine prescription that lasted for at least 6 months (long-BTD). Recorded diagnosis of substance addiction and disorders (Odds Ratio (95% CI) = 22.14 (21.88-22.41), P = 2.8 × 10-116), tobacco use disorder (OR (95% CI) = 23.4 (23.13-23.68), P = 4.5 × 10-111), and bipolar disorder (OR(95% CI) = 9.70 (9.48-9.92), P = 1.3 × 10-91), among others, were associated with longer BTD. The PGS of OUD and several OUD co-morbid conditions were associated with any buprenorphine prescription. A higher PGS for OUD (OR per SD increase in PGS (95%CI) = 1.43(1.16-1.77), P = 0.0009), loneliness (OR(95% CI) = 1.39(1.13-1.72), P = 0.002), problematic alcohol use (OR(95%CI) = 1.47(1.19-1.83), P = 0.0004), and externalizing disorders (OR(95%CI) = 1.52(1.23 to 1.89), P = 0.0001) was significantly associated with long-BTD. Associations between BTD and the PGS of depression, chronic pain, nicotine dependence, cannabis use disorder, and bipolar disorder did not survive correction for multiple testing. Longer BTD is associated with diagnoses of psychiatric and somatic conditions in the EHR, as is the genetic score for OUD, loneliness, problematic alcohol use, and externalizing disorders.

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway.

OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

Reimagine the ICU: Healthcare Professionals' Perspectives on How Environments (Can) Promote Patient Well-Being.

OBJECTIVE: This study aims (1) to understand the needs and challenges of the current intensive care unit (ICU) environments in supporting patient well-being from the perspective of healthcare professionals (HCPs) and (2) to explore the new potential of ICU environments enabled by technology. BACKGROUND: Evidence-based design has yielded how the design of environments can advocate for patient well-being, and digital technology offers new possibilities for indoor environments. However, the role of technology in facilitating ICU patient well-being has been unexplored. METHOD: This study was conducted in two phases. First, a mixed-method study was conducted with ICU HCPs from four Dutch hospitals. The study investigated the current environmental support for care activities, as well as the factors that positively and negatively contribute to patient experience. Next, a co-creation session was held involving HCPs and health technology experts to explore opportunities for technology to support ICU patient well-being. RESULTS: The mixed-method study revealed nine negative and eight positive patient experience factors. HCPs perceived patient emotional care as most challenging due to the ICU workload and a lack of environmental support in fulfilling patient emotional needs. The co-creation session yielded nine technology-enabled solutions to address identified challenges. Finally, drawing from insights from both studies, four strategies were introduced that guide toward creating technology to provide holistic and personalized care for patients. CONCLUSION: Patient experience factors are intertwined, necessitating a multifactorial approach to support patient well-being. Viewing the ICU environment as a holistic unit, our findings provide guidance on creating healing environments using technology.

Failed back surgery syndrome successfully ameliorated with Chiropractic Biophysics® structural rehabilitation improving pain, disability as well as sagittal and coronal balance: a Chiropractic Biophysics® case report with a 6†year follow-up.

[Purpose] To present the case of the amelioration of chronic pain and disability in a patient suffering from failed back surgery syndrome. [Participant and Methods] A 27-year-old male with chronic low back pain was treated with a Coflex® intra-spinous instrument, however, it was removed shortly after due to poor outcome including worsening pain and disability. Radiographic assessment revealed significant posterior translation of the thorax complicated by significant loss of the normal lumbar lordosis and a left lateral translated thoracic cage posture. Chiropractic Biophysics® technique was applied over a 5.5-month period leading to structural spine improvements as well as improved pain, Oswestry disability index (ODI) and quality of life (QOL). [Results] There was a 21 mm reduction in posterior thoracic translation, a 6.2° improvement in lumbar lordosis and a 16 mm reduction in lateral thoracic translation corresponding with improved ODI and QOL scores. A 6 year follow-up showed successful outcome despite some degenerative changes in the spine at the prior surgical level. [Conclusion] This case adds to the growing literature showing the efficacy of non-surgical spinal rehabilitative methods in improving outcomes in patients with spinal deformity and associated disabilities. This case also demonstrates necessity of the continued criterion standard of spinal radiography for biomechanical assessment.

Value of Adherence to Posttreatment Follow-Up Guidelines for Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: The utility of intensive posttreatment surveillance of head and neck squamous cell carcinoma (HNSCC) has been debated. The objective is to investigate adherence to the National Comprehensive Cancer Network (NCCN) posttreatment follow-up guidelines and assess the association with recurrence and survival. METHODS: A total of 452 patients diagnosed with HNSCC at an academic medical center in a socioeconomically disadvantaged, urban setting were categorized by adherence to NCCN follow-up guidelines. Survival analyses were conducted to study the association between adherence and the 5-year overall survival and disease-specific survival in the entire cohort and subset of patients with documented recurrence. RESULTS: We found that 23.5% of patients were adherent to NCCN follow-up guidelines in the first year after treatment, and 15.9% were adherent over 5 years. Adherence in the first year was significantly associated with 5-year overall survival (HR 0.634; 95% CI 0.443-0.906; p = 0.0124) and disease-specific survival (HR 0.556; 95% CI 0.312-0.992; p = 0.0470), but consistent adherence over 5 years did not show a significant association. Among the 21.7% of the cohort with recurrence, adherence was not associated with early-stage recurrence (AJCC stage I/II). In this subset, first year adherence was associated with improved disease-specific but not overall survival, and adherence over 5 years was not associated with survival. CONCLUSION: Adherence to NCCN follow-up guidelines in the first year after treatment was associated with a better chance of 5-year overall and disease-specific survival, but this significant association was not observed among those who demonstrated consistent adherence over 5 years. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:708-716, 2024.

Intermittent fasting disrupts hippocampal-dependent memory and norepinephrine content in aged male and female mice.

Intermittent fasting (IMF) is associated with many health benefits in animals and humans. Yet, little is known if an IMF diet affects mood and cognitive processing. We have previously identified that IMF in diet-induced obese males increases norepinephrine and dopamine content in the hypothalamus and increases arcuate neuropeptide Y (NPY) gene expression more than in ad libitum control males. This suggests that IMF may improve cognition through activation of the hindbrain norepinephrine neuronal network and reverse the age-dependent decline in NPY expression. Less is known about the association between anxiety and IMF. Although, in humans, IMF during Ramadan may alleviate anxiety. Here, we address the impact of IMF on anxiety-like behavior using the open field test, hippocampal-dependent memory using the Y-maze and spatial object recognition, and hippocampal-independent memory using novel object recognition in middle-aged male and female (12 mo) and aged male and female (18 mo) mice. Using ELISA, we determined norepinephrine (NE) content in the dorsal hippocampus (DH) and prefrontal cortex (PFC). We also investigated gene expression in the arcuate nucleus (ARC), the lateral hypothalamus (LH), and the locus coeruleus (LC). In IMF-treated females at both ages, we observed an improvement in spatial navigation although an impairment in spatial object orientation. IMF-treated females (12 mo) had a reduction and IMF-treated males (12 mo) displayed an improvement in novel object recognition memory. IMF-treated females (18 mo) exhibited anxiolytic-like behavior and increased locomotion. In the DH, IMF-treated males (12 mo) had a greater amount of NE content and IMF-treated males (18 mo) had a reduction. In the ARC, IMF-treated males (12 mo) exhibited an increase in Agrp and Npy and a decrease in Adr1a. In the ARC, IMF-treated males (18 mo) exhibited an increase in Npy and a decrease in Adr1a; females had a trending decrease in Cart. In the LH at 12 months, IMF-treated males had a decrease in Npy5r, Adr1a, and Adr1b; both males and females had a reduction in Npy1r. In the LH, IMF-treated females (18 mo) had a decrease in Hcrt. In the LC at both ages, mice largely exhibited sex effects. Our findings indicate that IMF produces alterations in mood, cognition, DH NE content, and ARC, LH, and LC gene expression depending on sex and age.

Alstoboonine, an Ulean-Type Indole Alkaloid from Alstonia boonei Leaves.

Alstonia boonei De Wild is a common plant in West Africa used in traditional medicine for various indications. While the stem bark has frequently been investigated, not much is known about the phytochemistry and bioactivity of the leaves. Within the current study, the major alkaloids of a hydroethanolic leaf extract were therefore isolated and characterized by MS, NMR, and ECD. This led to the identification of alstoboonine 1, a new ulean-type alkaloid, along with eight previously reported indole alkaloids, 15-hydroxyangustilobine A (2), 6,7-seco-angustilobine B (3), 6,7-seco-19,20-α-epoxyangustilobine B (4), alstrostine E (5), alstrostine C (6), alstrostine D (7), 12-methoxyechitamidine (8), and 19-oxo-12-methoxyechitamidine (9). 1 was moderately active in vitro against Plasmodium falciparum NF54 (IC50 6.9 µM), but inactive against other protozoan parasites (Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani). No significant cytotoxic effects were observed in L6 rat skeletal myoblast cells and MCF-7 breast cancer cells. Similarly, compounds 3 to 9 did not show cytotoxicity in MCF-7 cells. Due to the reported traditional use of the plant as an anthelmintic, the major alkaloids 2, 5, 6, and 8 were tested against the nematode Caenorhabditis elegans. Nematicidal effects were observed for 6 (LC50 400 µM), whereas 2, 5, and 8 were inactive.

Safety Assessment of Ginkgo biloba-Derived Ingredients as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 10 Ginkgo biloba-derived ingredients, which are most frequently reported to function in cosmetics as skin conditioning agents or antioxidants. The Panel reviewed the available data to determine the safety of these ingredients. Because final product formulations may contain multiple botanicals, each containing the same constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. The Panel was concerned about the presence of ginkgolic acid in cosmetics. Industry should use good manufacturing practices to limit impurities. The Panel concluded that 5 Ginkgo biloba leaf-derived ingredients are safe in the present practices of use and concentration described in this safety assessment when formulated to be non-sensitizing; data are insufficient to determine the safety of the remaining 5 ingredients under the intended conditions of use in cosmetic formulations.

Safety Assessment of Hops as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Humulus Lupulus (Hops) Extract (reported functions include antimicrobial agent and hair conditioning agent) and Humulus Lupulus (Hops) Oil (reported function is fragrance). The Panel reviewed the relevant data related to these ingredients. Because final product formulations may contain multiple botanicals, each containing the same constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. For these ingredients, the Panel was concerned about the presence of 8-prenylnaringenin, ß-myrcene, and quercetin in cosmetics, which could result in estrogenic effects, dermal irritation, and genotoxicity, respectively. Industry should use current good manufacturing practices to limit impurities and constituents of concern. The Panel concluded that Humulus Lupulus (Hops) Extract and Humulus Lupulus (Hops) Oil are safe in cosmetics in the present practices of use and concentration when formulated to be non-sensitizing.

Liver metastases of neuroendocrine tumors: Conventional transarterial chemoembolization and thermal ablation.

PURPOSE: To identify prognostic factors for patients with neuroendocrine liver metastases (NELM) undergoing conventional transarterial chemoembolization (c-TACE), microwave ablation (MWA), or laser interstitial thermotherapy (LITT) and to determine the most effective therapy regarding volume reduction of NELM and survival. MATERIALS AND METHODS: Between 1996 and 2020, 130 patients (82 men, 48 women) were treated with c-TACE, and 40 patients were additionally treated with thermal ablation. Survival was retrospectively analyzed using the Kaplan-Meier-method. Additional analyses were performed depending on the therapeutic intention (curative, palliative, symptomatic). Prognostic factors were derived using Cox regression. To find predictive factors for volume reduction in response to c-TACE, a mixed-effects model was used. RESULTS: With c-TACE, an overall median volume reduction of 23.5 % was achieved. An average decrease in tumor volume was shown until the 6th c-TACE treatment, then the effect stopped. C-TACE interventions were most effective at the beginning of c-TACE therapy, and treatment breaks longer than 90 days negatively influenced the outcome. Significant prognostic factors for survival were number of liver lesions (p = 0.0001) and type of therapeutic intention (p < 0.0001). Minor complications and one major complication occurred in 20.3 % of LITT and only in 8.6 % of MWA interventions. Complete ablation was observed in 95.7 % (LITT) and 93.1 % (MWA) of interventions. CONCLUSION: New prognostic factors were found for survival and volume reduction. Efficacy of c-TACE decreases after the 6th intervention and treatment breaks longer than 90 days should be avoided. With thermal ablation, a high rate of complete ablation was achieved, and survival improved. KEY POINTS: · Number of liver lesions and therapeutic intention are prognostic factors for survival.. · Regarding volume reduction, C-TACE is most effective at the beginning of treatment and longer treatment breaks should be avoided.. · With MWA and LITT, a high rate of complete ablation was achieved. MWA trends toward fewer complications than LITT in the treatment of NELM (p = 0.07)..

Establishment of the mechanism of purification and levigation of green chemistry-assisted biocomposites of red ochre (Gairika): synthesis, characterization, and antibacterial, prebiotic, antioxidant, and antacid activities of the traditional Ayurvedic medicine Laghu Sutashekhara Rasa.

Gairika (red ochre) has a long history of influencing human civilization. Gairika is a rich source of nutrients used for reproductive and brain health. Gairika is mentioned as an antacid drug in Indian Ayurvedic medicine under Laghu Sutashekhara Rasa (LSR). However, a detailed study on LSR has not been reported to date. In the present study, LSR was prepared, and a pharmaceutical SOP (standardization procedure) was reported to obtain batch-to-batch reproducibility. LSR was characterized using FTIR, XRD, SEM-EDX, and TGA analyses. LSR was tested in vitro for its antacid activity. Advanced instrumentation revealed that LSR formation produced symmetrical particles (5-8 µm) with kaolin, kaolinite, quartz, goethite, and hematite, along with the phytoconstituents of Goghrita (clarified cow's butter), Shunthi, and Nagawalli, as confirmed by GC-MS/MS analysis. The FTIR study revealed the formation of a chelating complex of goethite and hematite along with their phytoconstituents. XRD analysis confirmed the presence of kaolin, kaolinite, quartz, goethite, and hematite. Using in vitro antacid experiments, LSR and Shunthi demonstrated significant antacid activity as compared to antacid drugs and standards in the market, such as CaCO3. The DPPH assay revealed IC50 values of 12.16 ± 1.23 mg/mL, which is 0.0029 of Trolox-equivalent antioxidant activity. The inhibition (18 ± 4 mm) against pathogens (S. aureus, E. coli, P. aeruginosa, and B. subtilis) and the prominent growth of gut microbiota-supported strains (S. boulardii, L. paracasei, and L. plantarum) observed on LSR formulation were indicative of LSR application as a prebiotic. Here, the mechanism of purification and levigation mentioned in the classical literature of LSR was established. Overall, purification of Gairika with cow ghee and levigation with Nagawalli may enhance the solubility, bioavailability, and shelf-life of LSR through hydration and co-crystallization mechanisms. This is the first comprehensive report on the pharmaceutical validation of LSR and its characterization. The results of the present study could contribute to the development and reliable reproduction of LSR and the utility of environmental red ochre as a medicine in combination with Shunthi (Zingiber officinale Roxb.), as prescribed under Indian Ayurvedic medicine.

Phenylpropanoid-enriched broccoli seedling extract can reduce inflammatory markers and pain behavior.

BACKGROUND: Pain is a worldwide problem requiring an effective, affordable, non-addictive therapy. Using the edible plant broccoli, a growth protocol was developed to induce a concentrated combinatorial of potential anti-inflammatories in seedlings. METHODS: A growth method was utilized to produce a phenylpropanoid-rich broccoli sprout extract, referred to as Original Extract (OE). OE was concentrated and then resuspended for study of the effects on inflammation events. A rabbit disc model of inflammation and degeneration, and, a mouse model of pain behavior were used for in vivo and in vitro tests. To address aspects of mammalian metabolic processing, the OE was treated with the S9 liver microsome fraction derived from mouse, for use in a mouse in vivo study. Analytical chemistry was performed to identify major chemical species. Continuous variables were analyzed with a number of methods including ANOVA, and two-tailed t tests, as appropriate. RESULTS: In a rabbit spine (disc) injury model, inflammatory markers were reduced, and levels of regenerative markers were increased as a result of OE treatment, both in vivo and in vitro. In a mouse pain behavioral model, after treatment with S9 liver microsome fraction, the resultant extract significantly reduced early and late pain behavior in response to a pain stimulus. The OE itself reduced pain behavior in the mouse pain model, but did not achieve the level of significance observed for S9-treated extract. Analytical chemistry undertaken on the extract constituents revealed identities of the chemical species in OE, and how S9 liver microsome fraction treatment altered species identities and proportions. CONCLUSIONS: In vitro and in vivo results indicate that the OE, and S9-treated OE broccoli extracts are worthwhile materials to develop a non-opiate inflammation and pain-reducing treatment.

Osteopathic Manipulative Treatment for a Chronic Rotator Cuff Tear: A Case Report.

Rotator cuff tears, particularly involving the supraspinatus muscle and/or tendon, are highly prevalent among individuals engaged in repetitive shoulder motions. Occupations demanding constant and repetitive shoulder movements are especially susceptible to rotator cuff injuries, potentially leading to prolonged joint wear and tear and an increased likelihood of joint replacement. Considering the impact of social determinants of health, including access to healthcare and socioeconomic status, it is imperative to explore conservative treatment modalities that alleviate financial burdens and reduce lengthy recovery periods. In this report, we present a case of a 64-year-old female hairdresser diagnosed with a chronic partial thickness rotator cuff tear who remained unresponsive to physical therapy and chiropractic manipulation but exhibited improvement following osteopathic manipulative treatment. Additionally, osteopathic considerations and pertinent literature are reviewed to provide insight into the broader context of shoulder pain management.

Achieving consensus on psychosocial and physical rehabilitation management for people living with kidney disease.

Background: People living with chronic kidney disease (CKD) need to be able to live well with their condition. The provision of psychosocial interventions (psychological, psychiatric and social care) and physical rehabilitation management is variable across England, as well as the rest of the UK. There is a need for clear recommendations for standards of psychosocial and physical rehabilitation care for people living with CKD, and guidance for the commissioning and measurement of these services. The National Health Service (NHS) England Renal Services Transformation Programme (RSTP) supported a programme of work and modified Delphi process to address the management of psychosocial and physical rehabilitation care as part of a larger body of work to formulate a comprehensive commissioning toolkit for renal care services across England. We sought to achieve expert consensus regarding the psychosocial and physical rehabilitation management of people living with CKD in England and the rest of the UK. Methods: A Delphi consensus method was used to gather and refine expert opinions of senior members of the kidney multi-disciplinary team (MDT) and other key stakeholders in the UK. An agreement was sought on 16 statements reflecting aspects of psychosocial and physical rehabilitation management for people living with CKD. Results: Twenty-six expert practitioners and other key stakeholders, including lived experience representatives, participated in the process. The consensus (>80% affirmative votes) amongst the respondents for all 16 statements was high. Nine recommendation statements were discussed and refined further to be included in the final iteration of the 'Systems' section of the NHS England RSTP commissioning toolkit. These priority recommendations reflect pragmatic solutions that can be implemented in renal care and include recommendations for a holistic wellbeing assessment for all people living with CKD who are approaching dialysis, or who are at listing for kidney transplantation, which includes the use of validated measurement tools to assess the need for further intervention in psychosocial and physical rehabilitation management. It is recommended that the scores from these measurement tools be included in the NHS England Renal Data Dashboard. There was also a recommendation for referral as appropriate to NHS Talking Therapies, psychology, counselling or psychotherapy, social work or liaison psychiatry for those with identified psychosocial needs. The use of digital resources was recommended to be used in addition to face-to-face care to provide physical rehabilitation, and all healthcare professionals should be educated to recognize psychosocial and physical rehabilitation needs and refer/sign-post people with CKD to appropriate services. Conclusion: There was high consensus amongst senior members of the kidney MDT and other key stakeholders, including those with lived experience, in the UK on all aspects of the psychosocial and physical rehabilitation management of people living with CKD. The results of this process will be used by NHS England to inform the 'Systems' section of the commissioning toolkit and data dashboard and to inform the National Standards of Care for people living with CKD.

Cost-effectiveness analysis of the Geriatric Fracture Center (GFC) concept: a prospective multicentre cohort study.

INTRODUCTION: Geriatric Fracture Centers (GFCs) are dedicated treatment units where care is tailored towards elderly patients who have suffered fragility fractures. The primary objective of this economic analysis was to determine the cost-utility of GFCs compared with usual care centres. METHODS: The primary analysis was a cost-utility analysis that measured the cost per incremental quality-adjusted life-year gained from treatment of hip fracture in GFCs compared with treatment in usual care centres from the societal perspective over a 1-year time horizon. The secondary analysis was a cost-utility analysis from a societal perspective over a lifetime time horizon. We evaluated these outcomes using a cost-utility analysis using data from a large multicentre prospective cohort study comparing GFCs versus usual care centres that took place in Austria, Spain, the USA, the Netherlands, Thailand and Singapore. RESULTS: GFCs may be cost-effective in the long term, while providing a more comprehensive care plan. Patients in usual care centre group were slightly older and had fewer comorbidities. For the 1-year analysis, the costs per patient were slightly lower in the GFC group (-$646.42), while the quality-adjusted life-years were higher in the usual care centre group (+0.034). The incremental cost-effectiveness ratio was $18 863.34 (US$/quality-adjusted life-year). The lifetime horizon analysis found that the costs per patient were lower in the GFC group (-$7210.35), while the quality-adjusted life-years were higher in the usual care centre group (+0.02). The incremental cost-effectiveness ratio was $320 678.77 (US$/quality-adjusted life-year). CONCLUSIONS: This analysis found that GFCs were associated with lower costs compared with usual care centres. The cost-savings were greater when the lifetime time horizon was considered. This comprehensive cost-effectiveness analysis, using data from an international prospective cohort study, found that GFC may be cost-effective in the long term, while providing a more comprehensive care plan. A greater number of major adverse events were reported at GFC, nevertheless a lower mortality rate associated with these adverse events at GFC. Due to the minor utility benefits, which may be a result of greater adverse event detection within the GFC group and much greater costs of usual care centres, the GFC may be cost-effective due to the large cost-savings it demonstrated over the lifetime time horizon, while potentially identifying and treating adverse events more effectively. These findings suggest that the GFC may be a cost-effective option over the lifetime of a geriatric patient with hip fracture, although future research is needed to further validate these findings. LEVEL OF EVIDENCE: Economic, level 2. TRIAL REGISTRATION NUMBER: NCT02297581.